Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.
Genes Dev. 2020 Jul 1;34(13-14):989-1001. doi: 10.1101/gad.336891.120. Epub 2020 Jun 4.
Polymerases and exonucleases act on 3' ends of nascent RNAs to promote their maturation or degradation but how the balance between these activities is controlled to dictate the fates of cellular RNAs remains poorly understood. Here, we identify a central role for the human DEDD deadenylase TOE1 in distinguishing the fates of small nuclear (sn)RNAs of the spliceosome from unstable genome-encoded snRNA variants. We found that TOE1 promotes maturation of all regular RNA polymerase II transcribed snRNAs of the major and minor spliceosomes by removing posttranscriptional oligo(A) tails, trimming 3' ends, and preventing nuclear exosome targeting. In contrast, TOE1 promotes little to no maturation of tested U1 variant snRNAs, which are instead targeted by the nuclear exosome. These observations suggest that TOE1 is positioned at the center of a 3' end quality control pathway that selectively promotes maturation and stability of regular snRNAs while leaving snRNA variants unprocessed and exposed to degradation in what could be a widespread mechanism of RNA quality control given the large number of noncoding RNAs processed by DEDD deadenylases.
聚合酶和核酸外切酶作用于新生 RNA 的 3' 端，以促进其成熟或降解，但这些活性之间的平衡如何控制来决定细胞 RNA 的命运，目前仍知之甚少。在这里，我们确定了人类 DEDD 脱腺苷酶 TOE1 在区分剪接体中小核 (sn)RNA 的命运与不稳定的基因组编码的 snRNA 变体方面的核心作用。我们发现，TOE1 通过去除转录后寡 (A) 尾巴、修剪 3' 端和防止核 exosome 靶向，促进大多数和次要剪接体中所有由 RNA 聚合酶 II 转录的常规 snRNA 的成熟。相比之下，TOE1 对测试的 U1 变体 snRNA 的成熟促进作用很小或没有，而这些 snRNA 则被核 exosome 靶向。这些观察结果表明，TOE1 位于 3' 端质量控制途径的中心，该途径选择性地促进常规 snRNA 的成熟和稳定性，而将 snRNA 变体未加工并暴露于降解中，这可能是一种广泛的 RNA 质量控制机制，因为大量非编码 RNA 由 DEDD 脱腺苷酶处理。
